Exercise and Testosterone Therapy in Elderly Men With Physical Frailty

The primary aim of this study is to determine, in hypogonadal older men with physical frailty, whether exercise training combined with testosterone replacement therapy can improve skeletal muscle strength, and lean mass, to a greater degree than exercise training alone.

Study Overview

• Status: Completed
• Conditions: Hypogonadism; Hip Fracture; Physical Frailty; Elective Hip Replacement
• Intervention / Treatment: Drug: Transdermal Testosterone gel (1%); Behavioral: Supervised exercise training

Detailed Description

Decreases in physical abilities, including losses of strength, endurance, balance, and coordination are major causes of disability and loss of independence in older men. Such individuals are at high risk for injurious falls, hospitalization, and use of supportive services. Age-associated testosterone deficiency may contribute to deficits in muscle mass and strength that are common in this patient population.

The primary aim of this study is to determine, in hypogonadal older men with physical frailty, whether six months of exercise training combined with testosterone replacement therapy can improve skeletal muscle mass and skeletal muscle strength, to a greater degree than six months of exercise training alone.

Secondary study aims are to determine in hypogonadal older men with physical frailty, whether six months of exercise training combined with testosterone replacement therapy can improve physical function, bone mineral density, and quality of life, to a greater degree than six months of exercise training alone.

Comparison: Men age 65 years and older who meet criteria for physical frailty and have a serum testosterone level below 350 ng/dl are randomly assigned to one of two groups: 1) transdermal testosterone replacement therapy + supervised exercise training for six months vs. 2) inactive placebo gel + supervised exercise training for six months.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Male, age 65 years and older
• Total serum testosterone level < 350 ng/dl
• Total Modified Physical Performance Test Score <28

Exclusion Criteria:

• Inability to walk 50 feet independently
• Current use of estrogen, progestin, or androgen containing compound
• Diagnosis of dementia of severity sufficient to interfere with informed consent or compliance with the protocol, or a score of 11 or greater on the Short Blessed Test of Orientation, Memory and Concentration
• Visual or hearing impairments that interfere with following directions
• Cardiopulmonary disease (recent MI, unstable angina or CHF, etc.), neuromuscular impairments, or unstable medical condition that would contraindicate progressive resistance exercise training
• History of prostate cancer or hormone dependent neoplasia
• PSA level > 4 ng/ml
• Serum liver transaminase levels of greater than 2 standard deviations above normal
• Use of drugs for osteoporosis for less than 1 year
• Current participation in a vigorous exercise or weight-training program more than once per week
• History of sleep apnea requiring use of CPAP
• Uncontrolled thyroid disease
• Diagnosis of cancer within the past 5 years other than superficial skin cancer (squamous or basal cell)
• hematocrit > 50%
• AUA symptom score > 16.
• History of alcohol or substance abuse
• Presence of severe facial acne
• Active symptoms of depression with GDS score > 5 and symptoms severe enough to cause >5% weight loss in previous 3 months or interfere with research assessments

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Transdermal Testosterone gel (1%); Transdermal testosterone 1% gel (Androgel) provided as 2.5 gm and/or 5 gm gel packets with dose titration and monthly dose adjustments to achieve and maintain serum total testosterone level between 500-900 mg/dL. Gel to be applied daily by participants. Participants are blinded to the contents of the gel packets. Participants in this arm also perform supervised exercise training for 6 months.	Drug: Transdermal Testosterone gel (1%); Transdermal testosterone replacement therapy with Androgel(TM). Daily application of gel at 5 mg, 7.5 gm, or 10 gm for six months. Target serum total testosterone level between 500-900 ng/dl.; Other Names: Androgel; Behavioral: Supervised exercise training; Supervised exercise training performed on site at academic medical center exercise facility. Exercise training consisted of 2 months of flexibility, balance, treadmill walking, and physical therapy-type exercises, followed by 4 months of progressive resistance training.
Placebo Comparator: Placebo gel; Inactive topical gel identical in appearance to the active medication, provided in packets identical to the packaging for the active medication. Gel to be applied daily by participants. Participants are blinded to the contents of the gel packets. Participants in this arm also perform supervised exercise training for 6 months.	Behavioral: Supervised exercise training; Supervised exercise training performed on site at academic medical center exercise facility. Exercise training consisted of 2 months of flexibility, balance, treadmill walking, and physical therapy-type exercises, followed by 4 months of progressive resistance training.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Total Lean Body Mass	Total Lean Mass measured by Dual X-ray Absorptiometry (DXA)	Baseline and Six Months
Change in Skeletal Muscle Strength by 1-RM	One-repetition maximum strength for leg extension	Baseline and Six Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Isokinetic Leg Extension Torque at 0 Deg/Sec	Leg Extension Torque measured with Cybex dynamometer at 0 deg/sec	Baseline and Six Months
Change in Leg Extension Torque at 60 Deg/Sec	Leg Extension Torque measured with Cybex dynamometry at 60 deg/sec	Baseline and Six Months
Change in Total Body Fat Mass	Total Body Fat Mass as measured by DXA	Baseline and Six Months
Change in Femoral Bone Mineral Density (BMD)	Femoral Bone Mineral Density measured with Dual X-ray Absorptiometry (DXA)	Baseline and Six Months
Change in Total Modified Physical Performance (mPPT) Score	The Modified Physical Performance Test (mPPT) is a direct observational test that assesses multiple dimensions of physical function (basic and complex activities of daily living [ADL]) with different levels of difficulty. The test consists of 9 performance tasks. The total score range is 0-36 (min-max), with higher scores indicating better performance. Sub-scores are assigned for each of 9 item tasks; sub-score range is 0-4 (min-max) with higher scores indicating better performance. The sub-scores are summed to compute the total score.	Baseline and Six Months
Change in Serum Testosterone Level	Total Serum Testosterone Level (ng/mL)	Baseline and Six Months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Serum Prostate Specific Antigen (PSA) Level		Baseline and Six Months
Change in Hematocrit	Percentage of the volume of whole blood composed of Red Blood Cells	Baseline and Six Months
Change in Serum Total Cholesterol Level		Baseline and Six Months
Change in Serum HDL Cholesterol Level		Baseline and Six Months
Change in Serum LDL Cholesterol Level		Baseline and Six Months

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Collaborators: Solvay Pharmaceuticals
• Investigators: Principal Investigator: Ellen F. Binder, MD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: June 27, 2006
• First Submitted That Met QC Criteria: June 27, 2006
• First Posted (Estimate): June 29, 2006

Study Record Updates

• Last Update Posted (Actual): February 22, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Hip Fracture; Testosterone Replacement Therapy; Physical Frailty
• Additional Relevant MeSH Terms: Pathologic Processes; Fractures, Bone; Wounds and Injuries; Leg Injuries; Endocrine System Diseases; Gonadal Disorders; Femoral Fractures; Hip Injuries; Frailty; Hip Fractures; Hypogonadism; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: HSC 02-1108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO